Nuclear hormone receptors play key roles in multiple facets of development. Their abnormal expression is also strongly implicated in cancer of many forms. In the proposed studies, genes will be identified that are important for the in vivo function of one of the nuclear hormone receptors, the retinoid X receptor or RXR. Genetic screens in Drosophila will be performed to identify factors that interact with the Drosophila RXR homolog, usp. Usp, acting in conjunction with the EcR ecdysone receptor is critical for fly development. These screens will identify partner proteins that interact directly with usp as well as other critical components of the usp signaling pathway. It is hoped that this novel approach to studying RXR function will provide new and important insights into the mechanisms of nuclear hormone receptor action as well as the hormonal regulation of Drosophila development.